Mutation spectrum and frequency of the RHO gene in 248 Chinese families with retinitis pigmentosa

Mutations in the rhodopsin gene (RHO) are suggested to be the most common cause of autosomal dominant retinitis pigmentosa (RP). However, the exact spectrum and frequency of RHO mutations in different forms of RP has not been well defined, especially in Chinese populations. In this study, direct cycle sequencing was used to analyze all five coding exons and adjacent intronic regions of RHO in 248 Chinese probands with different forms of non X-linked RP. Eight heterozygous nucleotide changes were detected, including two novel mutations (c.628G>T, p.Val210Phe; c.945C>G, p.Asn315Lys) and six known mutations (c.527C>T, p.Ser176Phe; c.568G>T, p.Asp190Tyr; c.768_770delCAT, p.Ile256del; c.1040C>T, p.Pro347Leu; c.310G>A, p.Val104Ile; c.895G>T, p.Ala299Ser), in 14 probands (nine isolated cases, three from autosomal dominant families, and three from autosomal recessive families). Of the eight mutations, seven were missense changes and one was a small deletion. Six may be pathogenic mutations, and two others (c.310G>A, c.895G>T) may not be causative on their own. The p.Ala299Ser change was present in six of the 248 probands with RP but only in one of 384 normal controls, while the p.Val104Ile was present in two probands but none of the 384 controls. Our results demonstrate an overview of the spectrum and frequency of RP RHO mutations in a Chinese population and emphasize that RHO mutations in isolated RP are not uncommon.